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The World of MaTernal Immune Activation & EpigeneticS

4/6/2024

Val's Take/Conjecture

there is a LARGE DEVELOPMENTAL COMPONENT to the Neuro-Developmental Psychiatric Continuum.
It is focusing not so much on specific genes (although they may be important) as Maternal Immune Activation during Fetal Development.

BUT THAT IS NOT THE END OF THE STORY.

Epigenetics is playing a BIG ROLE on HIGHLY REACTIVE CELLS.

Additionally, Auto-Immune Diseases, especially Thyroid Disorders, affect a lot of people with "mental Illness" and EPIGENETICS is being viewed as a critical component in the understanding of Auto-Immune Diseases,

The epigenetics of autoimmunity | Cellular & Molecular Immunology (2011)

Alterations in the post-translational modification of histones and DNA methylation are the two major epigenetic mechanisms that may potentially cause a breakdown of immune tolerance and the perpetuation of autoimmune diseases.

Epigenomic signatures reveal mechanistic clues and predictive markers for autism spectrum disorder (2023)

Epigenetics and ADHD: Reflections on Current Knowledge, Research Priorities and Translational Potential (2022)

Epigenetic processes that regulate gene expression, such as DNA methylation, have emerged as a promising molecular system in the search for both biomarkers and mechanisms to address this challenge.

In this Current Opinion, we discuss the relevance of epigenetics (specifically DNA methylation) for ADHD research and clinical practice, starting with the current state of knowledge, what challenges we have yet to overcome, and what the future may hold in terms of methylation-based applications for personalized medicine in ADHD.

Additionally, people with "Autism" seem to be more at risk for Cancer, and cancer is more and more understood to have epigenetic components.

Epigenetics and Cancer - Introduction to Epigenetics (2021)
Alterations in chromatin function and epigenetic mechanisms are a hallmark of cancer. The disruption of epigenetic processes has been linked to altered gene expression and to cancer initiation and progression. Recent cancer genome sequencing projects revealed that numerous epigenetic regulators are frequently mutated in various cancers.

the new paradigm is getting stronger all the time

4/6/2024

Val's Take/Conjecture

The Normal Science of the DSM 5 is not worthless BUT it is not adequate to the task of our current mental health crisis and there are serious errors.
It became more and more apparent there was a lot we were missing:
- Maternal Immune Activation
- the Neuro-Developmental Psychiatric Continuum
- Dysregulation of Multiple Systems of the Body, and
- Mitochondrial Dysfunction.

From my perspective the EVIDENCE has been there well over a decade that Mental Health Clinical was on shaky ground.

our source the National Institute of Mental Health

On the other hand, there were no Interim Procedures and apart from someone like myself crying in the Colorado Wilderness, most professionals on all sides seem to be fine putting this Burden of Ignorance on very ill individuals.

That is UNETHICAL.

Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder (2023)

MIA [Maternal Immune Activation] is one of the common environmental risk factors for the onset of ASD during pregnancy. It induces an immune reaction in the pregnant mother’s body, resulting in further inflammation and oxidative stress in the placenta and fetal brain.

Psychopathology of attention deficit/hyperactivity disorder: from an inflammatory perspective. (2022)

A growing body of evidence shows that maternal inflammatory status during pregnancy is associated with diagnosis of ADHD in the offspring, whereas oxidative stress, inflammatory biochemical markers and immune-mediated diseases have been observed in individuals with ADHD

Oxidative Stress and Psychiatric Disorders: Evidence from the Bidirectional Mendelian Randomization Study (2022)

Mitochondrial Oxidative Stress—A Causative Factor and Therapeutic Target in Many Diseases (2021)
The main source of free radicals responsible for oxidative stress is mitochondrial respiration. The deleterious effects of ROS [Reactive Oxygen Species] on cellular biomolecules, including DNA, is a well-known phenomenon that can disrupt mitochondrial function and contribute to cellular damage and death, and the subsequent development of various disease processes.

maternal Immune Activation and Mitochondria

4/5/2024

Maternal Inflammation During Pregnancy and Offspring Brain Development: The Role of Mitochondria (2022)

In summary, we argue that mitochondrial function is a promising mechanism through which MIA/inflammation during pregnancy can affect the risk for neurodevelopmental and psychiatric disorders.

Elucidating the role of mitochondria as a mediator of MIA-induced alterations in brain development and neurodevelopmental disease risk may not only provide new insight into the pathophysiology of mental health disorders but may also offer new therapeutic targets

Metabolic aspects of mental health & Dietitians

3/30/2024

Val's Take/Conjecture

I think as the "METABOLIC" aspects of Mental Health come more into focus there's going to be a need for Dieticians to provide specialized care.

One of the challenges of being "NEURO-DIVERSE" is sometimes what works for everyone else doesn't work for you.
This is also why BIOMARKERS are so important --- as opposed to subjective symptom clusters. Of course, most mental health professionals are not relying on subjective symptom clusters because they want to.

A Ketogenic Diet is being promoted by Metabolic Mind and the Researchers at Harvard and other places for Bipolar Disorder, etc.
- There are plenty of CAVEATS to that, even as people are experiencing a range of outcomes with current treatments.

Getting PERSONALIZED, INDIVIDUAL Dietary Advice and Monitoring is likely to be very important.

Mission

Provide resources and support which empower Behavioral Health Nutrition (BHN) Members to excel in the areas of addictions, eating disorders, intellectual and developmental disabilities, mental health.

Vision

Optimize the physical and cognitive health of those we serve through nutrition education and behavioral health counseling.

Ketosis and the ketogenic diet

FAT Metabolism and ATP Production

3/24/2024

Today Show
How Following the Keto Diet Improved this Man's Mental Health

SIGNIFICANTLY, no one is claiming a Keto Diet is a CURE-ALL.

But there are reasons to believe it could help address some of the METABOLIC ASPECTS of Mental Illness. Keto is lower carbs, high fat and moderate protein.

Fat can lead to greater ATP Production. Is it heart healthy, maybe not.

People with Mental Illness are often faced with various "CATCH-22s" when it comes to treatment.

Metabolic Mind --- Feb. 22, 2024
New Harvard Study Explores Brain Energy Metabolism in Bipolar Disorder

Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes that generate energy and (2) anabolic processes where they serve as building blocks for other compounds.

In catabolism, fatty acids are metabolized to produce energy, mainly in the form of adenosine triphosphate (ATP). When compared to other macronutrient classes (carbohydrates and protein), fatty acids yield the most ATP on an energy per gram basis, when they are completely oxidized to CO2 and water by beta oxidation and the citric acid cycle.[2] Fatty acids (mainly in the form of triglycerides) are therefore the foremost storage form of fuel in most animals, and to a lesser extent in plants.

In anabolism, intact fatty acids are important precursors to triglycerides, phospholipids, second messengers, hormones and ketone bodies. For example, phospholipids form the phospholipid bilayers out of which all the membranes of the cell are constructed from fatty acids. Phospholipids comprise the plasma membrane and other membranes that enclose all the organelles within the cells, such as the nucleus, the mitochondria, endoplasmic reticulum, and the Golgi apparatus. In another type of anabolism, fatty acids are modified to form other compounds such as second messengers and local hormones. The prostaglandins made from arachidonic acid stored in the cell membrane are probably the best-known of these local hormones.

------Wikipedia

ATP, Parkinson's and the neuro-developmental/Psychiatric continuum

3/15/2024

"The use of oxygen enables a net production of 38 molecules of ATP from one molecule of glucose. Without oxygen, net production is only 2 molecules of ATP.

Because oxygen-requiring reactions (aerobic metabolism) take place only in the mitochondria, it’s clearly advantageous in terms of energy production for cells to contain mitochondria."

Reference:
11.6: Aerobic Metabolism and the Mitochondria - Medicine ...

Parkinson's Disease in now being viewed as a failure to produce ATP.

"ATP is essential in human activities and health. We hypothesize that maintaining ATP levels may help to preserve vulnerable brain cells in neurodegenerative diseases like Parkinson's disease (PD). For this purpose, we developed and tested two types of chemical compounds, one for limiting ATP consumption and the other for enhancing ATP production."

ATP Maintenance via Two Types of ATP Regulators ... - ScienceDirect

Parkinson's is interesting because we think of it as a disorder of mobility, but it also has PSYCHIATRIC SYMPTOMS.

Psychiatric Symptoms Associated With Parkinson Disease

Many nonmotor aspects of PD, including depression, drug-induced psychosis and impulse control disorders, cognitive impairment, anxiety, and sleep disturbances, are common and are associated with a variety of poor outcomes. 2 These nonmotor symptoms complicate the clinical management of the disorder and are significant determinants of poor quality of life for patients and their caregivers. 3

Are hallucinations a symptom of Parkinson's disease?

Hallucinations and delusions are potential complications of Parkinson’s disease (PD). They may be severe enough to be classified as PD psychosis. Hallucinations are perceptions that aren’t really there. Delusions are beliefs that aren’t based in reality. One example is paranoia that persists even when a person is presented with contrary evidence.

Parkinson’s Hallucinations: Delusions and More - Healthline

Currently we estimate the "normal" Brain uses 20% of the oxygen of the body --- the brain uses more oxygen than any other organ of the body.

AUTISM

Autism Spectrum Disorders: The Mitochondria Connection

ourworldandautism.com ›
Why are Autistic People So Tired? Exploring Fatigue in Autism

Sep 21, 2023 · Fatigue in autism can be caused by sleep problems, such as difficulties falling asleep or staying asleep. Additionally, sensory overwhelm, which is common in autism, can lead to

ADHD

Response variability in Attention-Deficit/Hyperactivity ...

"The immediate effects of deficient ATP production and slow restoration of ionic gradients across membranes of rapidly firing neurons have implications for daily functioning: For individuals with ADHD, performance efficacy would be enhanced if repetitive and lengthy effortful tasks were segmented to reduce concurrent demands for speed and accuracy of response (introduction of breaks into lengthy/effortful activities such as examinations, motorway driving, assembly-line production)."

www.verywellhealth.com › adhd-fatigue-8407263ADHD Fatigue: Understanding the Connection - Verywell Health
Jan 4, 2024 · Fatigue is a common symptom in those with ADHD. Fatigue often brings tiredness and stress and can lead to burnout. Though the exact cause can be unknown and vary from person

MOOD DISORDERS

More recent studies showed that a decrease in the astrocytic release of ATP in the prefrontal cortex and hippocampus is a major cause of mood disorders. It is an attractive hypothesis that compensatory increases in P2X7Rs in these areas of the brain are the immediate actuators of MD and BD.
www.frontiersin.org › articles › 10Frontiers | Pathological ATPergic Signaling in Major ...

www.ncbi.nlm.nih.gov › pmc › articles
The relationship between fatigue and psychiatric disorders ... (2009)

Fatigue and psychiatric disorders frequently occur comorbidly and share similar phenomenological features. There has been debate as to whether chronic fatigue, or neurasthenia, should be

SCHIZOPHRENIA

www.ncbi.nlm.nih.gov › pmc › articles
Schizophrenia as metabolic disease. What are the causes?
Jan 19, 2023 · Purigenic signaling as a mechanism is Schizophrenia. ATP and adenosine work as neurotransmitters. ATP plays the role of the excitatory transmitter, while adenosine plays the

trialsjournal.biomedcentral.com › articles › 10Assessment of the efficacy of a fatigue management therapy in ...
Sep 17, 2020 · First, lack of energy, one of the main characteristics of fatigue, is frequently encountered in individuals with schizophrenia. Second, fatigue is a common and severe symptom

The Neuro-Developmental - Psychiatric Continuum and "Successful aging"

2/16/2024

Bodies of People With Mental Illness Are Biologically Older Than Their Actual Age

Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder (2023)

1 Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Japan
2 United Graduate School of Child Development, Osaka University, Japan
3 Global Center for Medical Engineering and Informatics, Osaka University, Japan
4 Addiction Research Unit, Osaka Psychiatric Research Center, Osaka Psychiatric Medical Center, Osaka, Japan
5 SANKEN (Institute of Scientific and Industrial Research), Osaka University, Japan

In this review, we discuss the inflammation and oxidative stress in the pathophysiology of ASD, particularly focusing on maternal immune activation (MIA).

MIA is a one of the common environmental risk factors for the onset of ASD during pregnancy.

It induces an immune reaction in the pregnant mother’s body, resulting in further inflammation and oxidative stress in the placenta and fetal brain.

These negative factors cause neurodevelopmental impairments in the developing fetal brain and subsequently cause behavioral symptoms in the offspring.

3 Big Takeaways from the Research

Neuroscience News

Protein Key to Neuroprotection and Aging Discovered (Dec. 2023)

The study emphasizes the potential of this discovery for developing new therapies for age-related diseases and promoting successful nervous system aging.

Source: LSU

Scientists at LSU Health New Orleans’ Neuroscience Center of Excellence, led by Nicolas Bazan, MD, PhD, Boyd Professor and Director, have identified a new mechanism that regulates a protein key for cell survival.

It appears to protect against the excessive oxidative stress that precedes the development of neurodegenerative diseases of the brain and eye.

Results are published in the Nature journal, Cell Death & Disease.

Elovanoid-N34 modulates TXNRD1 key in protection against oxidative stress-related diseases (2023)

Lipid mediators in the regulation of innate and adaptive immunity (2023)

Emerging roles of innate and adaptive immunity in Alzheimer’s Disease (2022)

Lipids and cancer: emerging roles in pathogenesis, diagnosis and therapeutic intervention (2020)

More Hard Issues: Homicidality, SUICIDALITY and the Imperfect world of psychiatric medications

1/24/2024

Val's Take

Sometimes we think serious, potentially catastrophic mental illness is not in the middle and upper middle class suburbs --- but it is.
That was seemingly proven once again by the killing of a father by his thirty-something son with "schizophrenia" in Highlands Ranch.
One of the ideas that the parents seemingly had and that clinicians have historically had and even advocates had in the beginnings of the MENTAL HEALTH MOVEMENT ----- "JUST TAKE THE DAMN MEDICATION."
So if people find the medication helpful --- they generally are taking it, and they are generally lobbying to ensure access to the medication at a reasonable price.
One of the places you see this is for people where the GENERIC is NOT going to be an ADEQUATE SUBSTITUTE.
In some ways, the current Activist Mental Health Movement is made up of a significant percentage of people in which the medication didn't work that well or made things worse.
In addition to that, sometimes Executive Functioning may be so impaired that adhering to a medication regime is not realistic.
While I think it was idiosyncratic mental health patients that have pushed this issue, Clinicians are more and more sophisticated about this issue as well --- and will do genetic testing if it is available for that particular medication and are on the lookout for side effects that would indicate the discontinuation of that particular medication.

TedTalk --- David Anderson of Cal-Tech
Most Psychiatric Medications work on the Brain -- Globally --- NOT SPECIFIC NEURAL CIRCUITS -- that can do more harm than good.

Pharmacogenetic Information & News
How Does Genetic Testing for Psychiatric Medication Work? (2017)

BUT what if --- you don't have a current medication or treatment that will bring the person into a RANGE in which the person can function without being a danger to others, themselves or "gravely disabled"?

TWO THINGS:

We need some place safe for that person to live
- For some people that is a Secure Placement.
- It is not for most people
Even if it is a Secure Placement, it needs to be comfortable and the person needs to have the ability to work with Clinicians and Peers to develop their "STRENGTHS" which often are IDIOSYNCRATIC -- and accommodations and workarounds for Executive Functioning Issues.

Not acknowledging the complexity of psychiatric medication in 2024 and failure to provide "contingency planning" if the medication:

Doesn't work for the person or well enough
Makes things worse
The person can't manage the administration
It's not clear what treatment would work
Etc.

IS MAKING US LESS SAFE.

Neuro-Diversity, Metabolism, Diet and the Need for Precision Medicine

1/20/2024

So to me the important thing about "Maternal Immune Activation" is "DYSREGULATION" of MULTIPLE SYSTEMS OF THE BODY.

And one of the BIG KEYS to that is "MITOCHONDRIA."

Down Syndrome based on research from the University of Colorado School of Medicine is now being conceptualized as an IMMUNE DISORDER. See also Mayo Clinic on general Down Syndrome information.

Nobody is expecting Down Syndrome to be REVERSED by "DIET" alone.

High IQ Developmental Difference/Disorder --- the reality of that is not something we're really willing to accept. I'm not saying we should "ACCEPT IT and DO NOTHING" ---

But there can be much more of looking for a "QUICK FIX" --- that may in fact help --- may even be LIFE SAVING
Even as the Developmental Aspects are shrugged off, ignored or never appreciated in the first place.

October 25, 2023

Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression

Maternal Inflammation During Pregnancy and Offspring Brain Development:

The Role of Mitochondria

"The association between maternal immune activation (MIA) during pregnancy and risk for offspring neuropsychiatric disorders has been increasingly recognized over the past several years. "

Critical role of dysfunctional mitochondria and defective mitophagy in autism spectrum disorders (2021)

Affiliations

Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment & Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, People's Republic of China; Lhasa Guangsheng Hospital, Lhasa, People's Republic of China.

Translational Neuroscience:
Toward New Therapies

Chapter 3
Psychotic Disorders and the Neurodevelopmental Continuum

Michael J. Owen

"EMBO" stands for Excellence in the Life Sciences in Europe and Around the World

Metabolic Mind: Interview with Dr. Chris Palmer at Harvard.

One of the current big ideas in PSYCHIATRIC DISORDERS is around METABOLISM and a KETOGENIC DIET.

This is being promoted by a number of academics and organizations including METABOLIC MIND.

Above is an interview with Dr. Chris Palmer at Harvard. I find SOME of Dr. Palmer's ideas very interesting --- I am concerned that there is not an appreciation of some of the DEVELOPMENTAL ASPECTS of this.

Mental Illness & Metabolism

What are the basic rules for keto?

Keto basics

"The ketogenic diet is a very low carb, high fat diet that shares many similarities with the Atkins and low carb diets.

"It involves drastically reducing carbohydrate intake and replacing it with fat. This reduction in carbs puts your body into a metabolic state called ketosis.

"When this happens, your body becomes incredibly efficient at burning fat for energy. It also turns fat into ketones in the liver, which can supply energy for the brain (6Trusted Source).

"Ketogenic diets can cause significant reductions in blood sugar and insulin levels. This, along with the increased ketones, has some health benefits."

A DSM 5 Classification System that Isn't Good Enough

1/16/2024

Our current classification system contained in the DSM 5 is not supported by the research.

What is supported by the research is something much more DEVELOPMENTAL in which diagnostic categories are not fixed..
That has clinical, legal and policy ramifications.

Neurodevelopmental disorders (NDD) without boundaries: research and interventions beyond classifications (2023)

"Both genetic and environmental factors, along with clinical and imaging features, argue toward a continnum between NDD (Neuro-Developmental Disorders) but also with adult psychiatric presentations.

"This new paradigm could modify the therapeutic strategy, with the development of large-spectrum treatments or new psychotherapies addressing co-occuring symptoms."

December 12, 2023

The Ups and Downs of Bipolar Disorder

National Institute of Mental Health feature story on Josh Santana who was academically gifted, had ADHD and Bipolar Disorder.

King's College London
Thinking Twice About ADHD and Autism Spectrum Disorder (2019)

Autism and Beyond: Unveiling Overlapping Neurotypes

January 24, 2024

Key Facts:

The study found a substantial overlap in neurodivergence, with 76.2% of autistic children displaying traits of other neurotypes, including ADHD.

Over 55% of children assessed for autism might also meet the diagnostic threshold for ADHD, highlighting the necessity of holistic neurotype assessments.

Despite the clinical overlap, only 26% of children with additional traits were investigated for an underlying diagnosis, stressing the need for more comprehensive evaluation methods.

Source: University of Glasgow

Affiliations

1 GHU-Paris Psychiatrie et Neurosciences, Paris, France.
2 Excellence Centre for Autism and Neuro-Developmental Disorders, Child and Adolescent Psychiatry Department, Robert Debré Hospital, Paris Cité University, Paris, France.
3 Immunology, Immunopathology, Immunotherapy, INSERM U959, Sorbonne University, Paris, France.
4 Université de Paris, INSERM U1266, Institute of Psychiatry and Neuroscience of Paris, Paris, France.
5 Child and Adolescent Psychiatry Department, Saint-Etienne University Hospital and CNRS UMR 5229, Institute of Cognitive Neuroscience Marc Jeannerod, University Lyon 1, Bron, France.
6 Child Mind Institute, New York, USA.
7 Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France.
8 CHU Montpellier-Saint Eloi Hospital, University of Montpellier, Unit of Child and Adolescent Psychiatry (MPEA1), Montpellier, France.
9 Center for Research in Epidemiology and Population Health (CESP), INSERM U 1018, Paris-Saclay University, Villejuif, France.
10 Department of Pediatrics, Sainte Justine Hospital Research Center, University of Montreal, Montreal, QC, H4A3J1, Canada.
11 INSERM-UMR1163, Université Paris Cité, Institut Imagine, Paris, France.
12 Faculty of Medicine, University of Tours, Tours, France.
13 Autism and NDD GIS (GIS Autisme et Troubles du Neurodéveloppement), Paris, France.
14 Autism and NDD GIS (GIS Autisme et Troubles du Neurodéveloppement), Paris, France. [email protected].
15 Department of Psychiatry, McGill University, Montreal, Canada.

Science Up

Shared Genes & Psychiatric Disorders

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Translational Medicine Friday

The World of MaTernal Immune Activation & EpigeneticS

the new paradigm is getting stronger all the time

maternal Immune Activation and Mitochondria

Metabolic aspects of mental health & Dietitians

FAT Metabolism and ATP Production

ATP, Parkinson's and the neuro-developmental/Psychiatric continuum

The Neuro-Developmental - Psychiatric Continuum and "Successful aging"

More Hard Issues: Homicidality, SUICIDALITY and the Imperfect world of psychiatric medications

Neuro-Diversity, Metabolism, Diet and the Need for Precision Medicine

A DSM 5 Classification System that Isn't Good Enough

Neurodevelopmental disorders (NDD) without boundaries: research and interventions beyond classifications (2023)

Translational Medicine Friday

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